Ivermectin and albendazole coadministration: opportunities for strongyloidiasis control.

In 2020, WHO recognised the importance of strongyloidiasis alongside soil-transmitted helminths (STH) in their 2021-30 roadmap, which aspires to target Strongyloides stercoralis with preventive chemotherapy by use of ivermectin. Combination treatment with both albendazole, the primary drug used to treat STH, and ivermectin, would improve the efficiency of mass drug administration targeting both STH and S stercoralis. In this Personal View, we discuss the challenges and opportunities towards the development of an efficient control programme for strongyloidiasis, particularly if it is to run concurrently with STH control. We argue the need to define the prevalence threshold to implement preventive chemotherapy for S stercoralis, the target populations and optimal dosing schedules, and discuss the added benefits of a fixed-dose coformulation of ivermectin and albendazole. Implementation of an efficient control programme will require improvements to current diagnostics, and validation of new diagnostics, to target and monitor S stercoralis infections, and consideration of the challenges of multispecies diagnostics for S stercoralis and STH control. Finally, the evolution of ivermectin resistance represents a credible risk to control S stercoralis; we argue that genome-wide approaches, together with improved genome resources, are needed to characterise and prevent the emergence of resistance. Overcoming these challenges will help to reduce strongyloidiasis burden and enhance the feasibility of controlling it worldwide.

Sustainable Surveillance of Neglected Tropical Diseases for the Post-Elimination Era.

The World Health Organization's (WHO's) 2030 road map for neglected tropical diseases (NTDs) emphasizes the importance of strengthened, institutionalized "post-elimination" surveillance. The required shift from disease-siloed, campaign-based programming to routine, integrated surveillance and response activities presents epidemiological, logistical, and financial challenges, yet practical guidance on implementation is lacking. Nationally representative survey programs, such as demographic and health surveys (DHS), may offer a platform for the integration of NTD surveillance within national health systems and health information systems. Here, we describe characteristics of DHS and other surveys conducted within the WHO Africa region in terms of frequency, target populations, and sample types and discuss applicability for post-validation and post-elimination surveillance. Maximizing utility depends not only on the availability of improved diagnostics but also on better understanding of the spatial and temporal dynamics of transmission at low prevalence. To this end, we outline priorities for obtaining additional data to better characterize optimal post-elimination surveillance platforms.

Interpreting whole genome sequencing for investigating tuberculosis transmission: a systematic review.

BACKGROUND: Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions compared to traditional typing approaches. Many public health and clinical teams will increasingly use WGS to investigate clusters of potential pathogen transmission, making it crucial to understand the benefits and assumptions of the analytical methods for investigating the data. We aimed to understand how different approaches affect inferences of transmission dynamics and outline limitations of the methods. METHODS: We comprehensively searched electronic databases for studies that presented methods used to interpret WGS data for investigating tuberculosis (TB) transmission. Two authors independently selected studies for inclusion and extracted data. Due to considerable methodological heterogeneity between studies, we present summary data with accompanying narrative synthesis rather than pooled analyses. RESULTS: Twenty-five studies met our inclusion criteria. Despite the range of interpretation tools, the usefulness of WGS data in understanding TB transmission often depends on the amount of genetic diversity in the setting. Where diversity is small, distinguishing re-infections from relapses may be impossible; interpretation may be aided by the use of epidemiological data, examining minor variants and deep sequencing. Conversely, when within-host diversity is large, due to genetic hitchhiking or co-infection of two dissimilar strains, it is critical to understand how it arose. Greater understanding of microevolution and mixed infection will enhance interpretation of WGS data. CONCLUSIONS: As sequencing studies have sampled more intensely and integrated multiple sources of information, the understanding of TB transmission and diversity has grown, but there is still much to be learnt about the origins of diversity that will affect inferences from these data. Public health teams and researchers should combine epidemiological, clinical and WGS data to strengthen investigations of transmission.

Declaring a tuberculosis outbreak over with genomic epidemiology.

We report an updated method for inferring the time at which an infectious disease was transmitted between persons from a time-labelled pathogen genome phylogeny. We applied the method to 48 Mycobacterium tuberculosis genomes as part of a real-time public health outbreak investigation, demonstrating that although active tuberculosis (TB) cases were diagnosed through 2013, no transmission events took place beyond mid-2012. Subsequent cases were the result of progression from latent TB infection to active disease, and not recent transmission. This evolutionary genomic approach was used to declare the outbreak over in January 2015.